PROJECT SUMMARY The use of morphine and other opioids to treat pain commonly results in severe itch. The endogenous opioid system has been implicated in the pathophysiology and treatment of several forms of chronic itch. Clinical and experimental evidence suggest that opioid receptors in the central, rather than peripheral, nervous system play a role in mediating the itch sensation. In the primate nervous system, the spinothalamic tract (STT) plays a critical role in relaying itch information in the spinal cord. The long-term goal of this project is to understand the role of opioids in mediating the itch sensation in the central nervous system. The current aims are to determine whether activation of mu-opioid receptors (MORs) or k-opioid receptors (KORs) in the spinal cord affects the response properties of STT neurons which carry itch information. This project will test the hypothesis that MOR agonists which cause itch excite STT neurons which carry itch information, while KOR agonists which have been used to treat itch inhibit these same neurons. The experiments are designed test the effects of opioids and opioid receptor antagonists on responses of antidromically identified, physiologically characterized STT neurons in anesthetized monkeys using iontophoresis and bath application techniques. The proposed experiments have the potential to pave the way for development of more specific treatments for both pain and itch by elucidating the specific receptor subtypes involved in each in primates.